Cytosolic phospholipase A2-alpha expression in breast cancer is associated with EGFR expression and correlates with an adverse prognosis in luminal tumours.
AffiliationDepartment of Molecular Medicine, Royal College of Surgeons in Ireland, Education, and Research Centre, Beaumont Hospital, Dublin 9, Ireland.
MeSHAntineoplastic Agents, Hormonal/therapeutic use
Breast Neoplasms/drug therapy/*enzymology/pathology
Oligonucleotide Array Sequence Analysis
Receptor, Epidermal Growth Factor/*metabolism
Reverse Transcriptase Polymerase Chain Reaction
MetadataShow full item record
CitationBr J Cancer. 2011 Jan 18;104(2):338-44. Epub 2010 Nov 30.
JournalBritish journal of cancer
AbstractBACKGROUND: The eicosanoid signalling pathway promotes the progression of malignancies through the production of proliferative prostaglandins (PGs). Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) activity provides the substrate for cyclooxygenase-dependent PG release, and we have previously found that cPLA(2)alpha expression correlated with EGFR/HER2 over-expression in a small number of breast cancer cell lines. METHODS: The importance of differential cPLA(2)alpha activity in clinical breast cancer was established by relating the expression of cPLA(2)alpha in tissue samples from breast cancer patients, and two microarray-based gene expression datasets to different clinicopathological and therapeutic parameters. RESULTS: High cPLA(2)alpha mRNA expression correlated with clinical parameters of poor prognosis, which are characteristic of highly invasive tumours of the HER2-positive and basal-like subtype, including low oestrogen receptor expression and high EGFR expression. High cPLA(2)alpha expression decreased overall survival in patients with luminal cancers, and correlated with a reduced effect of tamoxifen treatment. The cPLA(2)alpha expression was an independent predictive parameter of poor response to endocrine therapy in the first 5 years of follow-up. CONCLUSION: This study shows a role of cPLA(2)alpha in luminal breast cancer progression, in which the enzyme could represent a novel therapeutic target and a predictive marker.
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